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评估 P 物质在脑肿瘤生长中的作用。

Evaluating the role of substance P in the growth of brain tumors.

机构信息

Adelaide Centre for Neuroscience Research and Discipline of Anatomy and Pathology, University of Adelaide, Adelaide, South Australia, Australia.

出版信息

Neuroscience. 2014 Mar 7;261:85-94. doi: 10.1016/j.neuroscience.2013.12.027. Epub 2013 Dec 27.

Abstract

Recent research has investigated the expression and secretion of neuropeptides by tumors, and the potential of these peptides to facilitate tumor growth and spread. In particular, substance P (SP) and its receptor NK1 have been implicated in tumor cell growth and evasion of apoptosis, although few studies have examined this relationship in vivo. The present study used both in vitro and in vivo models to characterize the role of SP in tumor pathogenesis. Immunohistochemical assessment of human primary and secondary brain tumor tissue demonstrated a marked increase in SP and its NK1 receptor in all tumor types investigated. Of the metastatic tumors, melanoma demonstrated particularly elevated SP and NK1 receptor staining. Subsequently, A-375 human melanoma cell line was examined in vitro and found to express both SP and the NK1 receptor. Treatment with the NK1 receptor antagonist Emend IV resulted in decreased cell viability and an increase in cell death in this cell line in vitro. An animal model of brain tumors using the same cell line was employed to assess the effect of Emend IV on tumor growth in vivo. Administration of Emend IV was found to decrease tumor volume and decrease cellular proliferation indicating that SP may play a role in tumor pathogenesis within the brain. We conclude that SP may provide a novel therapeutic target in the treatment of certain types of brain tumors, with further research required to determine whether the role of SP in cancer is tumor-type dependent.

摘要

最近的研究调查了肿瘤中神经肽的表达和分泌,以及这些肽促进肿瘤生长和扩散的潜力。特别是,P 物质(SP)及其受体 NK1 被认为与肿瘤细胞的生长和凋亡逃逸有关,尽管很少有研究在体内研究这种关系。本研究使用体内和体外模型来描述 SP 在肿瘤发病机制中的作用。对人类原发性和继发性脑肿瘤组织的免疫组织化学评估表明,在所研究的所有肿瘤类型中,SP 和其 NK1 受体均明显增加。在转移性肿瘤中,黑色素瘤显示出特别高的 SP 和 NK1 受体染色。随后,在体外检查了 A-375 人黑色素瘤细胞系,发现该细胞系表达 SP 和 NK1 受体。用 NK1 受体拮抗剂 Emend IV 处理可导致该细胞系体外细胞活力降低和细胞死亡增加。使用相同细胞系的脑肿瘤动物模型评估了 Emend IV 对体内肿瘤生长的影响。发现 Emend IV 的给药可减少肿瘤体积并减少细胞增殖,表明 SP 可能在脑内肿瘤发病机制中起作用。我们得出结论,SP 可能为治疗某些类型的脑肿瘤提供新的治疗靶点,需要进一步研究以确定 SP 在癌症中的作用是否取决于肿瘤类型。

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